4-羟基雌甾二醇1-N7-鸟嘌呤 | 178971-91-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 4-羟基雌甾二醇1-N7-鸟嘌呤
• 中文别名: 4-羟基雌二醇1-N7-鸟嘌呤
• 英文名称: 7-[4-hydroxyestradiol-1(α,β)-yl]guanine
• 英文别名: 4-Hydroxy Estradiol 1-N7-Guanine；2-amino-7-[(8R,9S,13S,14S,17S)-3,4,17-trihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-1-yl]-1H-purin-6-one
• CAS: 178971-91-0
• 化学式: C₂₃H₂₇N₅O₄
• 分子量: 437.498
• InChiKey: FRKBGPSXUBCIFE-URRUNNDYSA-N

物化性质

• 熔点：
  >250°C (dec.)
• 溶解度：
  DMSO（稍微加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟雌二醇 在 manganese(IV) oxide 作用下， 以 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 5.17h， 生成 4-羟基雌甾二醇1-N7-鸟嘌呤
  参考文献：
  名称：

  Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

  摘要：

  Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to DNA. Four estrogen-deoxyribonucleoside adducts were synthesized by reaction of estrone 3,4-quinone (E(1)-3,4-Q), 17 beta-estradiol 3,4-quinone (E(2)-3,4-Q), or estrone 2,3-quinone (E(1)-2,3-Q) with deoxyguanosine (dG) or deoxyadenosine (dA) in CH3CO2H/H2O (1:1). Reaction of E(1)-3,4-Q or E(2)-3,4-Q with dG produced specifically 7-[4-hydroxyestradiol-1(alpha,beta)-yl]guanine (4-OHE(1)-1(alpha,beta)-N7Gua) or 7-[4-hydroxyestradiol-1(alpha,beta)-yl]-guanine (4-OHE(2)-1(alpha,beta)-N7Gua), respectively, in 40% yield, with loss of deoxyribose. These two quinones did not react with dA, deoxycytidine, or thymidine. When E(1)-2,3-Q was reacted with dG or dA, N-2-(2 -hydroxyestron-6-yl)deoxyguanosine (2-OHE(1)-6-N(2)dG, 10% yield) and N-6-(2-hydroxyestron-6-yl)deoxyadenosine (2-OHE(1)-6-N(6)dA, 80% yield), respectively, were formed. These adducts provide insight into the type of DNA damage that can be caused by o-quinones of the catechol estrogens. The estrogen 3,4-quinones are expected to produce depurinating guanine adducts that are lost from DNA, generating apurinic sites, whereas the 2,3-quinones would form stable adducts that remain in DNA, unless repaired. The adducts reported here will be used as references in studies to elucidate the structure of estrogen adducts in biological systems.

  DOI：

  10.1021/tx960002q

文献信息

• Slow loss of deoxyribose from the N7deoxyguanosine adducts of estradiol-3,4-quinone and hexestrol-3′,4′-quinone.
  作者：Muhammad Saeed、Muhammad Zahid、Sandra J. Gunselman、Eleanor Rogan、Ercole Cavalieri

  DOI：10.1016/j.steroids.2004.09.011

  日期：2005.1

  A variety of evidence has been obtained that estrogens are weak tumor initiators. A major step in the multi-stage process leading to tumor initiation involves metabolic formation of 4-catechol estrogens from estradiol (E,) and/or estrone and further oxidation of the catechol estrogens to the corresponding catechol estrogen quinones. The electrophilic catechol quinones react with DNA mostly at the N-3 of adenine (Ade) and N-7 of guanine (Gua) by 1,4-Michael addition to form depurinating adducts. The N3Ade adducts depurinate instantaneously, whereas the N7Gua adducts depurinate with a half-life of several hours. Only the apurinic sites generated in the DNA by the rapidly depurinatingN3Ade adducts appear to produce mutations by error-prone repair. Analogously to the catechol estrogen-3.4-quinones, the synthetic nonsteroidal estrogen hexestrol- 3',4'-quinone (HES-3',4'-Q) reacts with DNA at the N-3 of Ade and N-7 of Gua to form deputinating adducts. We report here an additional similarity between the natural estrogen E-2 and the synthetic estrogen HES, namely, the slow loss of deoxyribose from the N7deoxyguanosine (N7dG) adducts formed by reaction of E-2-3.4-Q or HES-3'.4'-Q with dG. The half-life of the loss of deoxyribose from the N7dG adducts to form the corresponding 4-OHE2-I-N7Gua and 3'-OH-HES-6'-N7Gua is 6 or 8 h, respectively. The slow cleavage of this glycosyl bond in DNA seems to limit the ability of these adducts to induce mutations. (C) 2004 Elsevier Inc. All rights reserved.
• Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides
  作者：Douglas E. Stack、Jaeman Byun、Michael L. Gross、Eleanor G. Rogan、Ercole L. Cavalieri

  DOI：10.1021/tx960002q

  日期：1996.1.1

  Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to DNA. Four estrogen-deoxyribonucleoside adducts were synthesized by reaction of estrone 3,4-quinone (E(1)-3,4-Q), 17 beta-estradiol 3,4-quinone (E(2)-3,4-Q), or estrone 2,3-quinone (E(1)-2,3-Q) with deoxyguanosine (dG) or deoxyadenosine (dA) in CH3CO2H/H2O (1:1). Reaction of E(1)-3,4-Q or E(2)-3,4-Q with dG produced specifically 7-[4-hydroxyestradiol-1(alpha,beta)-yl]guanine (4-OHE(1)-1(alpha,beta)-N7Gua) or 7-[4-hydroxyestradiol-1(alpha,beta)-yl]-guanine (4-OHE(2)-1(alpha,beta)-N7Gua), respectively, in 40% yield, with loss of deoxyribose. These two quinones did not react with dA, deoxycytidine, or thymidine. When E(1)-2,3-Q was reacted with dG or dA, N-2-(2 -hydroxyestron-6-yl)deoxyguanosine (2-OHE(1)-6-N(2)dG, 10% yield) and N-6-(2-hydroxyestron-6-yl)deoxyadenosine (2-OHE(1)-6-N(6)dA, 80% yield), respectively, were formed. These adducts provide insight into the type of DNA damage that can be caused by o-quinones of the catechol estrogens. The estrogen 3,4-quinones are expected to produce depurinating guanine adducts that are lost from DNA, generating apurinic sites, whereas the 2,3-quinones would form stable adducts that remain in DNA, unless repaired. The adducts reported here will be used as references in studies to elucidate the structure of estrogen adducts in biological systems.